Clinical Predictors in Acute Optic Neuritis: Analysis Based on Clinical Trial Data

Küchlin S, Ihorst G, Heinrich SP, Farassat N, Márquez Neila P, Hug MJ, Albrecht P, Lagrèze WA. Ophthalmology. 2025;132(6):631-643. doi:10.1016/j.ophtha.2025.01.010

Question

Are there baseline clinical factors that predict visual outcomes 6 months after acute optic neuritis?

Background/Summary of Findings

Acute idiopathic and multiple sclerosis–associated optic neuritis is the most common optic neuropathy in young adults and often results in retinal ganglion cell death. Although the prompt use of high-dose glucocorticosteroids is the only guideline-based treatment, recent interest has arisen in the use of plasma exchange, especially when administered early (within 48 hours of symptom onset). Plasma exchange is, due to its cost, invasiveness, and associated burden, often not initiated until visual recovery is insufficient, which prolongs the time to administration. Accordingly, knowledge of clinical predictors is needed to facilitate shared decision-making and to allocate time-sensitive and costly resources.

This was a secondary analysis of the Treatment of Optic Neuritis with Erythropoietin study cohort (NCT01962571) involving a total of 103 patients presenting within 10 days of a first episode of acute unilateral optic neuritis as a clinically isolated syndrome with baseline high-contrast visual acuity less than or equal to 20/40 Snellen (logarithm of the minimum angle of resolution 0.3). Main outcome measures were independent predictors of high-contrast visual acuity, low-contrast letter acuity, visual-evoked potential P100 peak times, macular ganglion cell and inner plexiform layer thickness, and peripapillary retinal nerve fiber layer thickness at 6 months.

Potential predictors were selected based on literature research and experience and then computed initial linear regression models that each included 1 predictor together with the baseline value of the outcome of interest. The authors used a forward-selection approach to build a multiple regression model for each outcome. Because the trial medication of the Treatment of Optic Neuritis with Erythropoietin study (erythropoietin) had no effect on the visual system, they used pooled (treatment-agnostic) data for all analyses.

The results showed that on multiple regression, the most consistent predictors were higher baseline high-contrast visual acuity, which was associated with better outcomes across all measures except visual-evoked potential conduction time; male sex, which predicted worse outcomes for all measures except high-contrast visual acuity; and older age, which was linked to poorer functional outcomes.

The authors concluded that patients who are older, are male, and present with worse initial visual function may be at risk for worse clinical outcomes in acute optic neuritis.

Clinical Value/Implications

According to the authors, this knowledge may inform individual patient counseling, may facilitate patient selection for time-sensitive and invasive immunomodulatory treatments, and can be used to ensure balanced risk characteristics in clinical neuroprotection trials.

Long-Term Safety and Performance of a Suprachoroidal Pressure Sensor System: Results of the EYEMATE-SC Trial Follow-Up Study

Micheletti E, Mansouri K, Dick HB, Hoffmann EM, Mackert MJ, Weinreb RN, Szurman P; EYEMATE-SC Study Group. Long-Term Safety and Performance of a Suprachoroidal Pressure Sensor System: Results of the EYEMATE-SC Trial Follow-Up Study. Ophthalmology. 2025;132(7):775-784. doi:10.1016/j.ophtha.2025.01.021

Question

What is the long-term safety and performance of a suprachoroidal implantable diagnostic medical device designed for measuring intraocular pressure in patients with glaucoma that offers direct digitized intraocular pressure readings in millimeters of mercury

Background/Summary of Findings

Measurement of intraocular pressure is a critical component of glaucoma care, as it is the only modifiable risk factor influencing the onset and progression of the disease. The current paradigm of obtaining intraocular pressure is, however, limited. Intraocular pressure is measured at a single snapshot in time, often no more than 4 times per year. Evidence shows that intraocular pressure exhibits diurnal-nocturnal, short-term, and long-term fluctuations, with most intraocular pressure peaks occurring outside office hours. Glaucoma progression is impacted by both intraocular pressure fluctuation and by peak intraocular pressure. Given that clinically there is likely a lack of enough intraocular pressure information to understand what the optic nerve is exposed to, continuous monitoring of intraocular pressure may be able to explain the extent of disease and rates of progression better than a summary of office-hour intraocular pressure measurements over multiple visits.

This was a prospective, open-label, multicenter interventional trial including 22 eyes of 22 patients with open-angle glaucoma who received the EYEMATE-SC implant in conjunction with nonpenetrating glaucoma surgery. Long-term safety of the EYEMATE-SC suprachoroidal sensor was analyzed. All patients underwent 5 follow-up visits over a 24-month follow-up period, from month 12 to month 36 after implantation. Each visit consisted of a comprehensive examination, including intraocular pressure measurement with the EYEMATE-SC system and Goldmann applanation tonometry. The agreement between GAT and the EYEMATE-SC was analyzed using Bland-Altman analysis. Adverse events and device-related adverse events were recorded at all follow-up visits

Of 24 eligible patients of the EYEMATE-SC trial, 22 patients (mean age 65.0 ± 10.6 years, 54.5% female) were enrolled. The overall mean follow-up was 2.7 ± 0.6 years. Limits of agreement between Goldmann applanation tonometry and EYEMATE-SC IOP were -6.2 to 5.7 mm Hg (mean absolute difference of 2.3 mm Hg), with greatest concordance at 12 months (concordance correlation coefficient = 0.802, N = 22) and 18 months (concordance correlation coefficient = 0.854, N = 19). A difference of less than 5 mm Hg was recorded in less than 85% of the 86 paired measurements. No serious adverse events and device-related adverse events were recorded. Most common adverse events were raised intraocular pressure in 5 patients, reduced visual acuity in 3 patients, and cataract in 3 patients.

The authors concluded that this study demonstrates the long-term safety of the EYEMATE-SC system. No serious adverse events related to the EYEMATE-SC were observed. The agreement between the EYEMATE-SC and GAT was within the standard range of intraocular pressure–measuring methods set by regulatory agencies. The EYEMATE-SC system is well tolerated and accurate for self-measurement of intraocular pressure throughout the day.

Clinical Value/Implications

Currently, we remain naïve, in most cases, to the extent of intraocular pressure fluctuations and levels our patients experience. Reacting to minimal information may lead to overtreatment in some and undertreatment in others. Having a more complete picture of each individual’s intraocular pressure should allow us to provide more personalized and vision loss–preventive care. The safety of the EYEMATE-SC in this study demonstrates that there is a surgical option that has the potential for broader use.

Evaluating the Utility of Initial Examinations in Retinopathy of Prematurity: Proposal of FIRST-ROP Algorithm for a Medium-Risk Cohort

Altamirano F, Yuan M, Hoyek S, Hu D, Abidi M, Chaaya C, De Bruyn H, Fulton A, Mantagos IS, Wu C, Gise R, Gonzalez E, VanderVeen DK, Patel NA. Evaluating the Utility of Initial Examinations in Retinopathy of Prematurity: Proposal of FIRST-ROP Algorithm for a Medium-Risk Cohort. Ophthalmology. 2025;132(6):713-717. doi:10.1016/j.ophtha.2025.01.004

Question

What is the utility of the first or second examinations for retinopathy of prematurity in a medium-risk cohort of infants?

Background/Summary of Findings

With the rise in premature births and shortage of ophthalmologists caring for infants with retinopathy of prematurity in the United States, health care systems face mounting pressure to optimize screening practices without compromising patient safety. There is a concern that current retinopathy of prematurity screening practices may lead to overscreening in some subsets of infants. Several published algorithms have shown the potential to decrease the burden of retinopathy of prematurity examinations. However, these models warrant further evaluation because of limitations in accessibility and practical implementation. Furthermore, advancements in neonatal care, such as improved oxygen management, have decreased the risk of retinopathy of prematurity requiring treatment, although the impact on the overall incidence of severe retinopathy of prematurity remains complex.

This retrospective consecutive study included infants screened for retinopathy of prematurity between 2017 and 2023 at 3 different tertiary-level care neonatal intensive care units. It aimed to assess patients with medium-risk retinopathy of prematurity, defined as those who did not meet the criteria for microprematurity or nanoprematurity: at least 27 weeks’ gestational age and with a birth weight of 800 grams or more. The primary outcomes included the rates of retinopathy of prematurity and treatment-warranted retinopathy of prematurity, the presence of treatment-warranted retinopathy of prematurity at the first or second inpatient examinations, the number of inpatient examinations performed before the first retinopathy of prematurity diagnosis, and the overall number of inpatient examinations performed.

A total of 2004 neonates were screened for retinopathy of prematurity, among whom 1125 (56.1%) met the inclusion criteria. Of those, 237 neonates (21.1%) had retinopathy of prematurity. Eleven infants (1.0%) required treatment for active disease. The median postmenstrual age at first retinopathy of prematurity diagnosis was 35.3 weeks. The median postmenstrual age at stage 3 diagnosis was 39.3 weeks. The median postmenstrual age at first treatment was 39.6 weeks. The median number of inpatient examinations was 2.0 for traditional screening, 1.0 examination after eliminating the first retinopathy of prematurity inpatient examination, and 1.0 examination after eliminating the first and second retinopathy of prematurity examinations. No patients met type 1 retinopathy of prematurity treatment criteria at either the first or second inpatient examination. In this cohort, starting examinations at 34 weeks’ postmenstrual age could save 30.6% of inpatient examinations.

The authors proposed that given these results, the current screening algorithm be amended to start retinopathy of prematurity examinations at 34 weeks’ postmenstrual age for neonates born at 27 weeks’ gestational age and weighing 800 grams or more.

Clinical Value/Implications

An individualized approach to retinopathy of prematurity screening has the potential to reduce the potential burden of overscreening on the health care system and provide more optimal care for patients most likely to warrant treatment.

Risk of Glaucoma in Patients Without Diabetes Using a Glucagon-Like Peptide 1 Receptor Agonist

Vasu P, Dorairaj EA, Weinreb RN, Huang AS, Dorairaj SK. Risk of Glaucoma in Patients Without Diabetes Using a Glucagon-Like Peptide 1 Receptor Agonist. Ophthalmology. 2025;132(8):859-868. doi:10.1016/j.ophtha.2025.02.011

Question

How does glucagon-like peptide 1 receptor agonist use in obese patients without diabetes affect risk for primary open-angle glaucoma and ocular hypertension compared to alternative weight loss medications?

Background/Summary of Findings

Elevated body mass index as well as obesity have been found to increase the risk of glaucoma in various studies. Other studies have also demonstrated that weight loss has led to decreases in intraocular pressure, perhaps suggesting a potential role for weight loss in glaucoma management. Initially indicated as a treatment for individuals with type 2 diabetes, glucagon-like peptide 1 receptor agonists have recently been prescribed as a medication for weight loss. Beyond appetite suppression and glycemic control, this medication class has also exhibited neuroprotective and anti-inflammatory effects in the eye, with some authors proposing their use in reducing glaucomatous disease progression.

A retrospective cohort study of the TriNetX research network was conducted by analyzing patient data from January 2004 through December 2024 in individuals older than 60 years. Overall, 61 057 patients were included in the analysis. Cohorts were matched for baseline demographics, comorbidities, and medication use. Alternative medications included in the analysis were orlistat, phentermine-topiramate, bupropion-naltrexone, or setmelanotide. The risk for primary open-angle glaucoma was significantly less in the glucagon-like peptide 1 receptor agonist group at both year 3 (50.4% lower risk) and year 5 (58.5% lower risk) compared with alternative medications. Similarly, the risk for ocular hypertension was also significantly lower at year 3 (55.9%) and year 5 (65.8%) in the glucagon-like peptide 1 receptor agonist group. Risk for stroke, myocardial infarction, pulmonary embolism, and death were also reduced significantly in the individuals without diabetes taking this medication class.

Clinical Value/Implications

Beyond its intended role in weight loss, glucagon-like peptide 1 receptor agonists may also play a role in intraocular pressure reduction and glaucoma pathogenesis. The authors suggest that glucagon-like peptide 1 receptor agonists may have potential as a glaucoma therapy in the future. Further research is still needed; however, the findings of this study are promising and significantly relevant to medical and eyecare providers.

Risk of Progression of Nonproliferative to Proliferative Diabetic Retinopathy After Cataract Surgery

Loya A, Hussain ZS, Muayad J, Chauhan MZ, Soliman MK, Sallam AB. Risk of Progression of Nonproliferative to Proliferative Diabetic Retinopathy After Cataract Surgery. Ophthalmology. 2025;132(7):817-822. doi:10.1016/j.ophtha.2025.02.006

Question

Does modern cataract surgery influence progression from nonproliferative diabetic retinopathy to proliferative diabetic retinopathy in patients with type 2 diabetes?

Background/Summary of Findings

Patients with type 2 diabetes are often at higher risk for cataract surgery-related complications. Although phacoemulsification results in less inflammation and blood aqueous barrier disruption compared with older surgical methods, the concern remains for potential worsening of diabetic retinopathy in patients who undergo cataract surgery.

Data from the TriNetX research network were analyzed retrospectively for patients evaluated between June 2004 through June 2024, a period when phacoemulsification became the preferred cataract surgery method in the United States. Patients included in the analysis were 18 years or older with type 2 diabetes and any stage of nonproliferative diabetic retinopathy without macular edema. They were divided into 2 groups, patients who underwent routine cataract surgery and those who did not go through cataract surgery. Overall, 3589 patients were included in each of the study and control groups. There was a balanced representation of various minorities, hemoglobin A1c (average: ~8%) and age (average: ~67 years).

All analyses in the study demonstrated a consistent increased 1-year risk for vitreous hemorrhage and proliferative diabetic retinopathy in patients with nonproliferative diabetic retinopathy who had cataract surgery. One possible explanation is that disruption of the blood aqueous barrier and inflammation from cataract surgery is often more severe in diabetic patients compared with nondiabetic patients. In addition, diabetic eyes have been found to have elevated aqueous concentrations of angiogenic factors, such as VEGF isoform 165 and hepatocyte growth factors.

Clinical Value/Implications

This study highlights the importance of closely monitoring patients with type 2 diabetes and nonproliferative diabetic retinopathy following cataract surgery. In particular, patients in the study exhibited an elevated risk of conversion to proliferative diabetic retinopathy within 1 year of cataract surgery. Although there are no established guidelines for dilated fundus examination after uncomplicated cataract surgery, this study suggests that patients with existing retinopathy should be evaluated much sooner than their routine annual diabetic eye examination.

Allan KC, Joo JH, Kim S, Shaia J, Kaelber DC, Singh R, Talcott KE, Rachitskaya AV. Glucagon-Like Peptide-1 Receptor Agonist Impact on Chronic Ocular Disease, Including Age-Related Macular Degeneration. Ophthalmology. 2025;132(7):748-757. doi:10.1016/j.ophtha.2025.01.016

Question

Do glucagon-like peptide 1 receptor agonists influence the risk for age-related ocular diseases, such as cataracts, ocular hypertension, primary open-angle glaucoma, nonexudative age-related macular degeneration, and exudative age-related macular degeneration?

Background/Summary of Findings

Glucagon-like peptide 1 receptor agonists have recently become more widely recognized not only as a treatment for diabetes but also as a weight loss medication. The repurposing of medications for alternative diseases has become an efficient method for bringing new treatment options to providers and patients. The potential role of glucagon-like peptide 1 receptor agonists in ocular disease is an exciting area for research and investigation as they have been shown to promote anti-inflammatory, antioxidant, and antiapoptotic effects in other organ systems.

This study used a large electronic health record database (TriNetX) to assess the impact of this drug class on chronic ocular diseases, including macular degeneration, cataracts, and glaucoma. The other medication groups included metformin, insulin, statin, and aspirin. Overall, this retrospective large-scale cohort study included 9669 patients older than 60 years with glucagon-like peptide-1 receptor agonist use, a diagnosis of diabetes, and at least 5 years of follow-up. This retrospective cohort study demonstrated that glucagon-like peptide 1 receptor agonists were associated with a reduced hazard of nonexudative macular degeneration compared with metformin, insulin, statins, and aspirin. Furthermore, there was a lower risk for exudative macular degeneration in patients using glucagon-like peptide-1 receptor agonists compared with patients in the insulin, aspirin, and statin groups. Through its anti-inflammatory and antioxidant properties, this medication class may protect against retinal pigment epithelium damage and slow extracellular drusen deposition.

The study also observed a reduction in primary open-angle glaucoma in patients using glucagon-like peptide-1 receptor agonist compared with both metformin and aspirin groups. There was minimal impact on risk for cataract formation and ocular hypertension in glucagon-like peptide-1 receptor agonist users.

Clinical Value/Implications

The results of this study suggest a potential benefit of glucagon-like peptide 1 receptor agonists in reducing the risk for nonexudative and exudative macular degeneration. The study also supports recent studies that found a protective effect against glaucoma relative to other medications. More clinical trials are needed to further explore the impact of this medication on specific stages of macular degeneration; however, the studies thus far on glucagon-like peptide 1 receptor agonists have been promising and may indicate a potential future role for them in the treatment of various ocular diseases.